Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.
UNIST Central Research Facilities (UCRF), Ulsan National Institute of Science and Technology, Ulsan 44919, Korea.
Mol Cells. 2023 Jun 30;46(6):374-386. doi: 10.14348/molcells.2023.2181. Epub 2023 Apr 20.
Thermal stress induces dynamic changes in nuclear proteins and relevant physiology as a part of the heat shock response (HSR). However, how the nuclear HSR is fine-tuned for cellular homeostasis remains elusive. Here, we show that mitochondrial activity plays an important role in nuclear proteostasis and genome stability through two distinct HSR pathways. Mitochondrial ribosomal protein (MRP) depletion enhanced the nucleolar granule formation of HSP70 and ubiquitin during HSR while facilitating the recovery of damaged nuclear proteins and impaired nucleocytoplasmic transport. Treatment of the mitochondrial proton gradient uncoupler masked MRP-depletion effects, implicating oxidative phosphorylation in these nuclear HSRs. On the other hand, MRP depletion and a reactive oxygen species (ROS) scavenger non-additively decreased mitochondrial ROS generation during HSR, thereby protecting the nuclear genome from DNA damage. These results suggest that suboptimal mitochondrial activity sustains nuclear homeostasis under cellular stress, providing plausible evidence for optimal endosymbiotic evolution via mitochondria-to-nuclear communication.
热应激会引起核蛋白的动态变化以及相关生理学变化，这是热休克反应（HSR）的一部分。然而，核 HSR 如何精细调节细胞内稳态仍不清楚。在这里，我们发现线粒体活性通过两条不同的 HSR 途径在核蛋白稳态和基因组稳定性中发挥重要作用。线粒体核糖体蛋白（MRP）耗竭增强了 HSR 期间 HSP70 和泛素的核仁颗粒形成，同时促进受损核蛋白和核质转运受损的恢复。线粒体质子梯度解偶联剂的处理掩盖了 MRP 耗竭的作用，这表明氧化磷酸化参与了这些核 HSR。另一方面，MRP 耗竭和活性氧（ROS）清除剂在 HSR 期间非加性地减少了线粒体 ROS 的产生，从而保护核基因组免受 DNA 损伤。这些结果表明，亚最佳的线粒体活性在细胞应激下维持核内稳态，为通过线粒体到核的通讯进行最佳共生进化提供了合理的证据。
